The general objective of this research is to determine the three-dimensional geometries of biologically active macromolecules and to correlate these geometries with their function and evolution. The structures of several proteins will be examined by X-ray crystallographic methods. Specific proteins now being studied include dihydrofolate reductase from E. coli, L. casei, R. rubrum cytochrome c2 and yeast peroxidase, for each of which a model has already been constructed. Also being investigated are the structures of chicken and R-plasmid dihydrofolate reductase.